Alzheimer’s drug debate heats up yet again

The 6.5 million Americans living with Alzheimer’s, the neurodegenerative disease that slowly robs people of their memories, are waiting for an effective treatment. Lecanemab, the second of two new Alzheimer’s drugs to receive accelerated Food and Drug Administration approval, is the first treatment to clearly show signs of slowing of the disease’s progress.

But lecanemab, like its predecessor aducanumab, is proving controversial. The Alzheimer’s community applauded the new drug, with the Alzheimer’s Association describing it as a “milestone achievement.” Some experts, too, celebrated the FDA’s decision as a step forward. But other Alzheimer’s researchers questioned the treatment’s target, suggesting that our understanding of the disease mechanism lags behind the rush to treatment.

Both lecanemab (sold as Leqembi) and aducanumab (sold as Aduhelm) reduce the buildup of amyloid plaques in the brains of Alzheimer’s patients. The “amyloid hypothesis” claims that the accumulation of those protein plaques drives cognitive decline and other hallmark symptoms of Alzheimer’s.

Lecanemab, which received FDA approval on Jan. 6, slowed cognitive decline by 27 percent in phase 3 trials for participants who took the drug for 18 months compared to those who took a placebo. There were safety concerns that require further study, including brain swelling in 12.5 percent of those who took the medicine.  Amyloid-related imaging abnormalities, MRI-detected brain irregularities associated with swelling or bleeding, were found in 21 percent of participants treated with the drug.

Peter Pitts, president of the Center for Medicine in the Public Interest, believes the FDA approval of lecanemab signals its continued commitment to awarding innovation. He also stressed that Alzheimer’s patients want this new drug.

Dr. Cheyn Onarecker is a family medicine doctor practicing in Oklahoma City and a member of the Christian Medical and Dental Associations. Onarecker highlighted the health risks, including brain bleeding and swelling and recommended the drug be used with caution until follow-up studies are conducted.

Opponents of the new drug say its effect is marginal and not worth the risks. Jorge Barrio, professor emeritus in pharmacology at the University of California, Los Angeles, thinks the slowing of cognitive decline for lecanemab phase 3 trial participants was marginal. “Probably a cup of coffee would do better,” he said.

In an open letter, Barrio and 11 other scientists explained why they think the 27 percent slowing of decline reported in the phase 3 trial is misleading.  They noted the study excluded nearly 60 percent of Alzheimer’s patients after initial screening because they didn’t fit the inclusion criteria. They also pointed out a disparity between men and women, with a 43 percent effect observed in men versus a 12 percent effect in women.

Barrio is one of a cohort of scientists who have long vocalized opposition to the amyloid hypothesis, arguing it lacks proof. None of the therapeutics targeting amyloid plaque developed over the years has provided significant benefit to Alzheimer’s patients. Barrio explained that amyloid plaque buildup can occur with age. Some elderly people have amyloid buildup throughout their brains but never develop any Alzheimer’s symptoms.

Both Barrio and Dr. Abass Alavi, co-author of the open letter and professor of radiology and neurology at the University of Pennsylvania, accuse pharmaceutical companies Eisai and Biogen of foul play. Barrio believes they are taking advantage of Alzheimer’s patients and their families, who are desperate to try anything. “Biogen just wants to get [its] stocks to become stronger and stronger. They don’t care about what happens to these poor patients,” said Alavi.

Onarecker thinks it’s too cynical to attribute the new drug’s development to pharmaceutical companies’ greediness. He argued that the FDA serves to mitigate pharmaceutical companies’ worst motivations by objectively weighing a new drug’s risks and benefits.

After treating many patients with Alzheimer’s in his practice, Onarecker recognizes how difficult the disease can be for patients and their loved ones. He said it can feel as if these patients have lost their dignity. But as Christians, he said, we know that our dignity does not lie in our physical state, but in our identity as God’s image-bearers.